Abstract
Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 % that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.
| Original language | English |
|---|---|
| Pages (from-to) | 341-350 |
| Number of pages | 10 |
| Journal | Breast Cancer Research and Treatment |
| Volume | 158 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2016 Jul 1 |
| Externally published | Yes |
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Keywords
- Breast histology
- Lobular involution
- Menarche
- Menopause
- SNP
- TDLU
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue. / Oh, Hannah; Bodelon, Clara; Palakal, Maya; Chatterjee, Nilanjan; Sherman, Mark E.; Linville, Laura; Geller, Berta M.; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.; Papathomas, Daphne; Patel, Deesha A.; Xiang, Jackie; Clare, Susan E.; Visscher, Daniel W.; Mies, Carolyn; Hewitt, Stephen M.; Brinton, Louise A.; Storniolo, Anna Maria V.; He, Chunyan; Garcia-Closas, Montserrat; Chanock, Stephen J.; Gierach, Gretchen L.; Figueroa, Jonine D.
In: Breast Cancer Research and Treatment, Vol. 158, No. 2, 01.07.2016, p. 341-350.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ages at menarche- and menopause-related genetic variants in relation to terminal duct lobular unit involution in normal breast tissue
AU - Oh, Hannah
AU - Bodelon, Clara
AU - Palakal, Maya
AU - Chatterjee, Nilanjan
AU - Sherman, Mark E.
AU - Linville, Laura
AU - Geller, Berta M.
AU - Vacek, Pamela M.
AU - Weaver, Donald L.
AU - Chicoine, Rachael E.
AU - Papathomas, Daphne
AU - Patel, Deesha A.
AU - Xiang, Jackie
AU - Clare, Susan E.
AU - Visscher, Daniel W.
AU - Mies, Carolyn
AU - Hewitt, Stephen M.
AU - Brinton, Louise A.
AU - Storniolo, Anna Maria V.
AU - He, Chunyan
AU - Garcia-Closas, Montserrat
AU - Chanock, Stephen J.
AU - Gierach, Gretchen L.
AU - Figueroa, Jonine D.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 % that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.
AB - Reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. Younger age at menarche and older age at menopause have been previously related to lower levels of TDLU involution. To determine a possible genetic link, we examined whether single-nucleotide polymorphisms (SNPs) previously established in genome-wide association studies (GWAS) for ages at menarche and menopause are associated with TDLU involution. We conducted a pooled analysis of 862 women from two studies. H&E tissue sections were assessed for numbers of TDLUs and acini/TDLU. Poisson regression models were used to estimate associations of 36 menarche- and 21 menopause-SNPs with TDLU counts, acini counts/TDLU, and the product of these two measures, adjusting for age and study site. Fourteen percent of evaluated SNPs (eight SNPs) were associated with TDLU counts at p < 0.05, suggesting an enrichment of associations with TDLU counts. However, only menopause-SNPs had >50 % that were either significantly or nonsignificantly associated with TDLU measures in the directions consistent with their relationships shown in GWAS. Among ten SNPs that were statistically significantly associated with at least one TDLU involution measure (p < 0.05), seven SNPs (rs466639: RXRG; rs2243803: SLC14A2; rs2292573: GAB2; rs6438424: 3q13.32; rs7606918: METAP1D; rs11668344: TMEM150B; rs1635501: EXO1) were associated in the consistent directions. Our data suggest that the loci associated with ages at menarche and menopause may influence TDLU involution, suggesting some shared genetic mechanisms. However, larger studies are needed to confirm the results.
KW - Breast histology
KW - Lobular involution
KW - Menarche
KW - Menopause
KW - SNP
KW - TDLU
UR - http://www.scopus.com/inward/record.url?scp=84976275062&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84976275062&partnerID=8YFLogxK
U2 - 10.1007/s10549-016-3859-z
DO - 10.1007/s10549-016-3859-z
M3 - Article
VL - 158
SP - 341
EP - 350
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -